First description of an acinic cell carcinoma of the breast in a BRCA1 mutation carrier: a case report

Abstract

BackgroundAcinic cell carcinoma (ACC) is a rare malignant epithelial neoplasm characterized by the presence of malignant tubular acinar exocrine gland structures. Diagnosis is generally made in salivary glands and in the pancreas. ACC of the breast has been reported in few cases only. Carriers of inherited mutations in the BRCA1 gene are prone to the development of breast cancer, mainly invasive ductal or medullary type carcinomas. We describe for the first time a BRCA1 mutation carrier with a diagnosis of ACC of the breast.Case presentationThe patient developed an invasive ductal carcinoma (IDC) at the age of 40 years and an ACC in the contralateral breast at 44 years. Immunohistochemical examination of the ACC revealed a triple negative status (i.e., negativity for estrogen receptor, progesterone receptor and HER2 protein) and positivity for p53. Using a combination of loss of heterozygosity (LOH) and sequencing analyses, the loss of the wild-type BRCA1 allele was detected in both the ACC and the IDC. In addition, two different somatic TP53 mutations, one in the ACC only and another one in the IDC only, were observed.ConclusionBoth the immunohistochemical and molecular features observed in the ACC are typical of BRCA1-associated breast cancers and suggest an involvement of the patient’s germline mutation in the disease. The occurrence of rare histological types of breast cancers, including malignant phyllodes tumor, atypical medullary carcinoma and metaplastic carcinoma, in BRCA1 mutation carriers has been already reported. Our findings further broaden the spectrum of BRCA1-associated breast malignancies.

The repertoire of somatic genetic alterations of acinic cell carcinomas of the breast: an exploratory, hypothesis‐generating study

“…The presence of poorly differentiated tumors adjacent to ACCs is not an uncommon finding in the breast [7,23] and it has also been reported in the context of ACCs of the salivary glands [54]. The non-ACC components of the mixed cases included in this study were all high-grade, highly proliferative triple-negative breast carcinomas (Figure 2 and Table 2).…”

“…The truncating BRCA1 somatic mutation identified in case 17 was coupled with LOH of the wild-type allele (Figure 3) providing evidence of complete loss of BRCA1 . Given this observation and the fact that an ACC has been reported in a patient with a BRCA1 germline mutation [23], we investigated whether the patients included in this study harbored germline disease-causing mutations affecting DNA-repair related breast cancer susceptibility genes, including BRCA1 , BRCA2 , PALB2 , RAD51C , RAD51D , BRIP1 and FAM175A . This analysis revealed the presence of a germline frame-shift mutation of BRCA1 (E23*) in case 10.…”

“…Furthermore, breast adenoid cystic carcinomas display low levels of chromosomal instability and fewer copy number alterations than high-grade TNBCs, and patterns of somatic genetic alterations distinct from those of low-grade invasive ductal carcinomas [14,20,22]. A recent case report demonstrated that breast ACCs may develop in the context of BRCA1 germline mutation carriers; genetic analysis of one such case revealed loss of heterozygosity (LOH) of the BRCA1 locus and the presence of a TP53 somatic mutation, akin to other types of BRCA1 -related breast cancers [23]. Our group has recently demonstrated by Sanger sequencing analysis that, like common types of TNBC, TP53 mutations are found in up to 80% of breast ACCs [24].…”

Acinic cell carcinoma of breast: morphologic and immunohistochemical review of a rare breast cancer subtype

“…The phenomenon of tubules with central luminal extracellular “colloid-like” material was described as “MGA-like” in several articles [4,7,13], whereas other articles interpreted the appearance as suggestive of true MGA [22]. Interestingly, in 11 cases where collagen IV and laminin immunohistochemistry was performed, these MGA or MGA-like areas were entirely negative for these basement membrane markers in 8 cases [7,13,19,24]. In the remaining 3 cases [12] (including the 2 cases reported in this article), very focal positivity was noted.…”

Acinic Cell Carcinoma

“…Acinic cell carcinoma has also been reported to develop in the lacrimal gland [ 44 ] and lung [ 21 , 49 ]. A limited number of breast ACCs have been reported [ 14 , 24 , 32 , 35 , 62 , 64 , 76 ], and recently also one case has been reported in a BRCA1 mutation carrier [ 68 ]. Bilateral acinic cell carcinoma is very rare, and less than 20 cases have been reported [ 25 ].…”